PURPOSE: To evaluate the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics of thalidomide in patients with advanced hepatocellular carcinoma (HCC). METHODS: Patients with advanced HCC who were not feasible for definitive local therapy were eligible. Patients were enrolled in a cohort of three to receive thalidomide twice daily for 1 week to determine the MTD. Intra-patient dose escalation was permitted. Pharmacokinetic studies were performed at the first dose level and repeated at the second dose level of each patient. RESULTS: Fifteen patients were accrued at four dose levels with the starting dose range 100-400 mg/day. Two patients at 400 mg/day experienced DLT (grade 3 angioedema and dyspnea, respectively). The MTD of twice-daily schedule was determined as 300 mg/day. The mean steady-state maximal blood concentration and mean steady-state area under the curve had a trend toward positive correlation, but non-linear proportionate, to the daily dose of thalidomide. Pharmacokinetic parameters are comparable for patients of Child-Pugh's A and B. Apparent mild, transient drug-induced transaminitis was early onset, self-limited, which occurred in 30.7% of patients. Serum hepatitis B or C viral titers was largely not affected. CONCLUSION: The absorption and elimination of thalidomide are not significantly different in HCC patients with compensated or decompensated hepatic dysfunction.
PURPOSE: To evaluate the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics of thalidomide in patients with advanced hepatocellular carcinoma (HCC). METHODS:Patients with advanced HCC who were not feasible for definitive local therapy were eligible. Patients were enrolled in a cohort of three to receive thalidomide twice daily for 1 week to determine the MTD. Intra-patient dose escalation was permitted. Pharmacokinetic studies were performed at the first dose level and repeated at the second dose level of each patient. RESULTS: Fifteen patients were accrued at four dose levels with the starting dose range 100-400 mg/day. Two patients at 400 mg/day experienced DLT (grade 3 angioedema and dyspnea, respectively). The MTD of twice-daily schedule was determined as 300 mg/day. The mean steady-state maximal blood concentration and mean steady-state area under the curve had a trend toward positive correlation, but non-linear proportionate, to the daily dose of thalidomide. Pharmacokinetic parameters are comparable for patients of Child-Pugh's A and B. Apparent mild, transient drug-induced transaminitis was early onset, self-limited, which occurred in 30.7% of patients. Serum hepatitis B or C viral titers was largely not affected. CONCLUSION: The absorption and elimination of thalidomide are not significantly different in HCC patients with compensated or decompensated hepatic dysfunction.
Authors: R Biffi; F Orsi; M G Zampino; A Chiappa; N Fazio; F De Braud; G Bonomo; L Monfardini; P D Vigna; F Luca; L Bodei; M Bartolomei; G Catalano; M C Leonardi; M Ferrari; B Andreoni; A Goldhirsch; G Paganelli; R Orecchia Journal: Ecancermedicalscience Date: 2008-05-02
Authors: Helen B Stone; Eric J Bernhard; C Norman Coleman; James Deye; Jacek Capala; James B Mitchell; J Martin Brown Journal: Transl Oncol Date: 2016-02 Impact factor: 4.243